Rapid effect of nicotine intake on neuroplasticity in non-smoking humans

Jessica Grundey, Nivethida Thirugnanasambandam, Kim Kaminsky, Anne Drees, Angela C Skwirba, Nicolas Lang, Walter Paulus, Michael A Nitsche, Jessica Grundey, Nivethida Thirugnanasambandam, Kim Kaminsky, Anne Drees, Angela C Skwirba, Nicolas Lang, Walter Paulus, Michael A Nitsche

Abstract

In various studies nicotine has shown to alter cognitive functions in non-smoking subjects. The physiological basis for these effects might be nicotine-generated modulation of cortical structure, excitability, and activity, as mainly described in animal experiments. In accordance, a recently conducted study demonstrated that application of nicotine for hours via nicotine patch in non-smoking humans alters the effects of neuroplasticity-inducing non-invasive brain stimulation techniques on cortical excitability. Specifically, nicotine abolished inhibitory plasticity independent from the focality of the stimulation protocol. While nicotine prevented also the establishment of non-focal facilitatory plasticity, focal synapse-specific facilitatory plasticity was enhanced. These results agree with a focusing effect of prolonged nicotine application on facilitatory plasticity. However, since nicotine induces rapid adaption processes of its receptors, this scenario might differ from the effect of nicotine in cigarette smoking. Thus in this study we aimed to gain further insight in the mechanism of nicotine on plasticity by exploring the effect of nicotine spray on non-focal and focal plasticity-inducing protocols in non-smoking subjects, a fast-acting agent better comparable to cigarette smoking. Focal, synapse-specific plasticity was induced by paired associative stimulation (PAS), while non-focal plasticity was elicited by transcranial direct current stimulation (tDCS). Forty eight non-smokers received nicotine spray respectively placebo combined with one of the following protocols (anodal tDCS, cathodal tDCS, PAS-25, and PAS-10). Corticospinal excitability was monitored via motor-evoked potentials elicited by transcranial magnetic stimulation (TMS). Nicotine spray abolished facilitatory plasticity irrespective of focality and PAS-10-induced excitability diminution, while tDCS-derived excitability reduction was delayed and weakened. Nicotine spray had thus a clear effect on neuroplasticity in non-smoking subjects. However, the effects of nicotine spray differ clearly from those of prolonged nicotine application, which might be due to missing adaptive nicotinic receptor alterations. These results enhance our knowledge about the dynamic impact of nicotine on plasticity, which might be related to its heterogenous effect on cognition.

Keywords: PAS; neuroplasticity; nicotine; non-smokers; tDCS.

Figures

Figure 1
Figure 1
This figure illustrates the experimental protocol of our study. At the beginning of the session baseline measurements (BL) were performed and followed by administration of either nicotine spray or placebo spray. After 10 min baseline (BL) motor cortical excitability was redetermined via TMS-induced motor-evoked potentials (MEP). One of the four excitability-inducing protocols were then applied (atDCS, ctDCS, PAS-10, PAS-25). After-measurements started immediately after the application of the protocols, and were conducted every 5 min for the first 30 min, then every 30 min up to 120 min for both sessions. MEP amplitudes were also recorded the next morning and next evening for the nicotine spray sessions.
Figure 2
Figure 2
(A,B) Nicotinergic impact on transcranial direct current stimulation (tDCS) induced neuroplasticity. Shown are the graphs with motor evoked potentials (MEP) standardized to the baseline on the Y-axis plotted against different time points post-intervention on the X-axis. Filled symbols indicate statistically significant deviations from baseline and asterisks indicate significant differences between the control and nicotine conditions (Student’s t-test, paired, two-tailed, p < 0.05). nm, Next morning; ne, next evening; plc, placebo. Tb, Baseline MEP-amplitude before begin of the stimulation protocols (standardized). Error bars indicate standard error of mean.
Figure 3
Figure 3
(A,B) Nicotinergic impact on paired associative stimulation (PAS) induced neuroplasticity. Shown are the graphs with motor evoked potentials (MEP) standardized to the baseline on the Y-axis plotted against different time points post-stimulation on the X-axis. Filled symbols indicate statistically significant deviations from baseline and asterisks indicate significant differences between the placebo medication and nicotine conditions (Student’s t-test, paired, two-tailed, p < 0.05). nm, Next morning; ne, next evening; plc, placebo. Tb, Baseline MEP-amplitude before begin of the stimulation protocols (standardized). Error bars indicate standard error of mean.
Figure 4
Figure 4
(A,B) Comparison of TMS-stimulator intensity and MEP amplitudes before and after nicotine spray administration. Shown are the TMS-stimulator intensity as percentage of maximum stimulator output (A) and respective motor evoked potentials [MEP amplitudes in mV; (B)] before and after nicotine spray administration for the different interventions (atDCS, ctDCS, PAS-25, PAS-10). ns, Non significant; mV, millivolt.

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